Management of type 2 diabetes in patients with heart failure

Opinion statement  Diabetes mellitus and heart failure (HF) commonly coexist, and together these conditions are associated with increased morbidity and mortality compared with either condition alone. Although the optimal treatment strategy to achieve glucose control in HF patients with type 2 diabetes has not been well studied, given the common coexistence of these conditions and the need to adequately treat hyperglycemia to prevent microvascular complications, it is important for clinicians to understand the potential implications of diabetic therapy in patients with established HF. Until recently, metformin was contraindicated in patients with HF because of the potential risk of lactic acidosis; however, recent retrospective studies of metformin use in HF patients have shown that this medication may be used safely and indeed may be beneficial in patients with stable HF. The association between thiazolidinediones (TZDs) and HF remains controversial, but recent prospective randomized trials of TZD use in HF patients suggest that worsening volume retention associated with these agents may lead to worsening of HF symptoms. The recently developed incretin-based therapies, such as exenatide and sitagliptin, also have not been extensively studied in HF populations; however, small pilot studies of glucagon-like peptide-1 have shown potential promise in the treatment of diabetic patients with HF. Although they may be difficult to perform, future randomized controlled trials are needed to establish optimal treatment goals and strategies in this population.     

Excess risk of hospitalisation for heart failure among people with type 2 diabetes

Aims/hypothesis

Type 2 diabetes is an established risk factor for heart failure, but age-specific data are sparse. We aimed to determine excess risk of heart failure, based on age, glycaemic control and kidney function in comparison with age- and sex-matched control individuals from the general population.

Methods

Individuals with type 2 diabetes registered in the Swedish National Diabetes Registry 1998–2012 (n?=?266,305) were compared with age-, sex- and county-matched control individuals without diabetes (n?=?1,323,504), and followed over a median of 5.6 years until 31 December 2013.

Results

We identified 266,305 individuals with type 2 diabetes (mean age 62.0 years, 45.3% women) and 1,323,504 control individuals. Of the individuals with type 2 diabetes and control individuals, 18,715 (7.0%) and 50,157 (3.8%) were hospitalised with a diagnosis of heart failure, respectively. Comparing individuals with diabetes with those in the control group, men and women with type 2 diabetes who were younger than 55 years of age had HRs for hospitalisation for heart failure of 2.07 (95% CI 1.73, 2.48) and 4.59 (95% CI 3.50, 6.02), respectively, using analyses adjusted for socioeconomic variables and associated conditions. Younger age, poorer glycaemic control and deteriorating renal function were all associated with increased excess risk of heart failure in those with type 2 diabetes compared with the control group. However, people with diabetes who were ≥75 years and without albuminuria or with good glycaemic control (HbA_1c ≤52 mmol/mol [≤6.9%]) had a similar risk of hospitalisation for heart failure as control individuals in the same age group.

Conclusions/interpretation

Men and women aged <55 years with type 2 diabetes are at markedly elevated excess risk of heart failure. The excess risk declined with age, but persisted even with good glycaemic control. However, among those who were 75 years and older, diabetic individuals with well controlled glucose levels or without albuminuria had a risk of heart failure that was on a par with individuals without diabetes.

     

Twelve-year trends in pharmacologic treatment of type 2 diabetes among patients with heart failure in the United States

We conducted a cross-sectional analysis using a database from commercial health plans in the United States to describe trends in the use of antidiabetic medications among patients with type 2 diabetes and heart failure (HF) from 2006 through 2017. We used loop diuretic dose as a surrogate for HF severity (mild HF 0-40 mg/day, moderate-severe HF >40 mg/day). We assessed antidiabetic medication dispensing in the 90 days following HF diagnosis. Over the 12-year period, we identified an increase in the use of metformin (39.2% vs. 62.6%), dipeptidyl peptidase-4 inhibitors (DPP-4i) (0.5% vs. 17.1%) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) (0.0% vs. 9.0%), but a decrease in the use of sulphonylureas (47.8% vs. 27.8%) and thiazolidinediones (TZDs) (31.7% vs. 5.3%). In 2017, patients with moderate-severe HF more commonly used insulin (43.1%); a majority of mild HF patients used metformin (62.8%). A proportion of patients with moderate-severe HF used TZDs (4.4%). Among patients with diabetes and HF, the use of metformin and DPP-4i rapidly increased, but a proportion of patients with moderate-severe HF continued to use TZDs. Despite their promising cardiovascular safety profile, SGLT-2i use remains limited.     

Loop diuretic use among patients with heart failure and type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors

AimsTo compare loop diuretic use in patients with comorbid heart failure (HF) and type 2 diabetes (T2D) newly initiated on sodium glucose cotransporter-2 inhibitors (SGLT2Is) versus other oral anti-glycemic agents (AGAs).MethodsThis analysis used 2013–2015 MarketScan Medicare Supplemental claims data. HF and T2D patients were identified and SGLT2I users were propensity score matched to other AGA users. The mean daily dose of loop diuretics in furosemide equivalents was ascertained. For those not on baseline loop diuretics, new use was compared between cohorts. For those on baseline loop diuretics, we assessed patterns of use (increased dose, decreased dose, stable dose, no longer using) at 12-months.ResultsA total of 750 SGLT2I users were matched to 750 other AGA users. The distribution of loop diuretic use at mean doses of 0 mg (i.e., no use), ≤20 mg, >20 mg–40 mg, >40 mg–80 mg and >80 mg/day did not differ between cohorts at baseline or 12-months (p > 0.05 for both). SGLT2I use was associated with less new loop diuretic use (22.7% [79/348] vs. 34.0% [132/388]; p = 0.001). For those on loop diuretics at baseline (n = 764), patterns of use at 12-months did not differ between cohorts (p = 0.14).ConclusionsNew loop diuretic use was less frequent among SGLT2I users; however, patterns of loop diuretic use did not differ between cohorts in those on loop diuretics at baseline.     

卡维地洛对糖尿病并发冠心病心力衰竭患者的影响

目的观察卡维地洛对2型糖尿病并发冠心病心力衰竭患者的心功能及血脂、血糖、胰岛素抵抗的影响。方法2型糖尿病并发冠心病心力衰竭患者105例,根据常规治疗基础上加用卡维地洛与否分为治疗组和对照组。治疗12个月,观察卡维地洛对心功能及血脂、血糖、胰岛素抵抗的指标变化。结果①卡维地洛用量平均（12±4）mg/d。②对心功能及心室重构的影响:与对照组相比,治疗组12个月左室射血分数较对照组显著升高[（50±4）%与（45±6）%,P<0.01],左室收缩末容积下降[（166±41）ml与（184±38）ml,P<0.01]。NYHA分级也明显改善。③治疗12个月后治疗组与对照组血脂及空腹血糖、胰岛素、胰岛素抵抗指数均无明显变化。结论卡维地洛能明显改善2型糖尿病并发冠心病心力衰竭患者的心功能和心室重构,而对其血脂及空腹血糖、胰岛素、胰岛素抵抗指数无明显影响,可以安全应用于2型糖尿病并发冠心病心力衰竭患者。     

Survival and hospitalization in heart failure patients with or without diabetes treated with beta-blockers

BACKGROUND: Physicians are still concerned about prescribing beta-blockers in diabetic patients with heart failure. METHODS: In the outcome research study (the Beta-Blockers in Patients With Congestive Heart Failure: Guided Use in Clinical Practice [BRING-UP] study), the responsible clinicians could decide whether to start beta-blocker treatment and which agent to use. A total of 3091 patients were enrolled by 202 cardiologic centers: 25% of the recruited patients were already on beta-blockers, 28% started treatment at the enrollment visit, and 47% were not started on beta-blockers. RESULTS: The 1-year mortality, hospitalization rate, and the combined end point of mortality or hospitalization were higher in diabetic patients (15.8% versus 10.9%; relative risk [RR] = 1.44; 95% confidence intervals [CI] 1.16-1.78, P =.001) (31.0% versus 24.0%; RR = 1.28; 95% CI 1.11-1.49; P =.0009) (40.5% versus 30.1%; RR = 1.35; 95% CI 1.19-1.51; P =.0001). The event-free analysis of the 4 groups (diabetic patients not treated with beta-blockers, diabetic patients treated with beta-blockers, nondiabetic patients not treated with beta-blockers, nondiabetic patients treated with beta-blockers) showed that patients treated with beta-blockers had a higher event-free probability than patients not treated with beta-blockers regardless the presence of diabetes (P <.0001). CONCLUSIONS: On the basis of post hoc analysis, diabetic patients with chronic heart failure benefit from beta-blockers even if at a lower degree. Thus, there are no justifications to avoid beta-blockers in heart failure patients in the presence of diabetes.     

Unmet needs among patients with type 2 diabetes and secondary failure to oral anti-diabetic agents

Secondary failure is defined as a deterioration of glucose control in patients with Type 2 diabetes on oral antidiabetic drugs (OAD), mainly due to the progressive decline in beta-cell function and reduction in insulin secretion. The consequent hyperglycemia is the most important determinant for the development of microvascular and macrovascular complications, so that an early recognition of this phenomenon can improve long-term outcomes. The recent lowering of target glycosylated hemoglobin (HbA1c) levels by international guidelines not only emphasises the importance of tight glycemic control, but also means that secondary failure to OAD will occur much sooner and is almost unavoidable. Accordingly, in the last years, new different therapeutic strategies were explored to improve the treatment of this condition. The aim of this review is to examine current approaches for treating patients with secondary failure, barriers to achieving and maintaining glycemic control, and recent evidence for emerging therapies which may represent a valid therapeutic option in subjects failing on oral hypoglycemic agents by acting mainly, but not only, at a beta-cell level. In particular, we will focus on the co-administration of OAD plus a novel drug class known as incretin mimetics (e.g. exenatide and liraglutide), which target insulin secretion, and on thiazolidinediones, which act on insulin resistance. Only incretin-mimetics have a lowering HbA1c action, due to the improvement in beta-cell function, which is coupled to significant weight loss. Even if these new options seem to improve the outcome of secondary failure, further investigation is needed to confirm positive results in the long term.     

Multimarker approach to risk stratification among patients with advanced chronic heart failure

BACKGROUND: Cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) each predict adverse cardiac events in chronic heart failure (CHF). However, little is known about the utility of these novel biomarkers of CHF in combination. HYPOTHESIS:: We hypothesized that simultaneous assessment of the three biomarkers would enable clinicians to stratify risk more effectively among patients with advanced CHF. METHODS: Measurements of the biomarkers were performed on 152 patients with symptomatic advanced CHF. Major adverse cardiac events during a median follow-up period of 186 days were determined. RESULTS: Univariate and multivariate analysis revealed that elevations of each biomarker were significant predictors of clinical outcome independently of clinical variables. When patients were categorized on the basis of the number of elevated biomarkers, patients with one, two and three elevated biomarkers respectively had a 2.7-(p = 0.125), 8.6- (p < 0.0001) and 23.4-(p < 0.0001) fold increase in the risk of adverse events. CONCLUSIONS: Simultaneous measurement of cTnI, hsCRP, and NT-proBNP could provide complementary information and a simple multimarker strategy that categorizes the patients with advanced CHF based on the number of elevated biomarkers, allowing rapid risk stratification in these patients.     

Albuminuria as a predictor of heart failure hospitalizations in patients with type 2 diabetes

BACKGROUND: Heart failure (HF) occurs more frequently and is a significant cause of mortality in diabetic patients. The purpose of the current study is to ascertain risk factors that are predictive of HF hospitalizations in type 2 diabetic patients. METHODS: Longitudinal observational study of type 2 diabetic patients with baseline diastolic blood pressures > or =80 mm Hg and no history of New York Heart Association class III-IV HF or a serum creatinine > or =2.5 mg/dL nested within a randomized clinical trial. The outcome measure of this study was the first occurrence of HF hospitalization over a 5-year follow-up period. RESULTS: Patients with overt albuminuria at baseline had a higher and earlier occurrence of HF hospitalizations than those with micro- or normoalbuminuria (13.6% versus 3.3%, odds ratio [OR]=3.1, 95% confidence interval [CI]=2.15-4.60, P<.0001). In the multiple logistic regression analyses, the presence of overt albuminuria (OR 5.4, 95% CI=2.3-12.5, P<.001), history of myocardial infarction (OR 4.6, 95% CI=1.6-13.1, P=.004) and a history of New York Heart Association Class I or II HF (OR 8.0, 95% CI=2.2-28.6, P=.0014) at baseline were independently associated with HF hospitalizations. CONCLUSIONS: Overt albuminuria predicts the occurrence of HF hospitalizations in type 2 diabetic patients. Thus early aggressive treatment of diabetic nephropathy should be investigated as a means of preventing of HF.